The goal of this project is to develop unique column packings for high-performance liquid chromatography. These new materials will allow the very fast separation and characterization of both small molecules of biological and pharmaceutical interest and very large biomolecular components that are not well handled by current technology. Previous studies by the PI have shown that superficially-porous silica microspheres (solid core and porous shell) permit very fast separations of macromolecules. Such particle structures are capable of very fast separations because of excellent mass transfer (kinetic) properties, combined with good sample loading characteristics. However, the original spray-drying preparation method used to prepare these particles resulted in uneven porous shells and unwanted totally-porous particles and therefore was abandoned. Preliminary experiments now indicate that with a new, different approach, silica cores can be coated with a polymeric coacervate containing a highly purified silica sol. Polymer elimination with subsequent processing produces ultra-pure, low acidity controlled surface porosity ("CSP") particles with a range of narrow pore sizes. Columns with CSP particle-based packings would be effective in reversed- phase and ion-exchange separations for monitoring large-scale purifications,, as rapid diagnostic tests, drug assays, characterizing fermentation broths, separating DNA fragments and many other life science applications requiring very fast, reliable, high-resolution measurements. The products of this proposal also are highly suited for use in HPLC-MS applications. The new products of this proposal will provide for superior methods to characterize a wide range of biologicals, including drugs, and enhance capabilities to study systems of current interest that involve biomacromolecular materials. For example, these products will be useful in genetic and proteomic studies, especially when multidimensional ("2-D") separations are required. [unreadable] [unreadable] [unreadable]